LiBF4-mediated conversion of aldehydes to gem-diacetates

Article abstract of DOI:10.1055/s-2002-22705

An efficient and highly selective method for the conversion of aldehydes to gem-diacetates is described using lithium tetrafluoroborate under mild reaction conditions. Due to the neutral reaction conditions, this method is compatible with acid-sensitive p

Full text of DOI:10.1055/s-2002-22705

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04
LETTER
LiBF -Mediated Conversion of Aldehydes to gem-Diacetates
4
L
J
iBF -me
.
diate
d
Conve
S
r
sion of Aldeh
.
ydes to gem
Y
-Diacetates adav, B. V. S. Reddy, Chenna Venugopal, T. Ramalingam*
4
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
E-mail: Chennavenu007@yahoo.com
Received 13 September 2001
various substituted aldehydes reacted well with acetic an-
hydride to give the corresponding acylals in high yields
Abstract: An efficient and highly selective method for the conver-
sion of aldehydes to gem-diacetates is described using lithium tet-
rafluoroborate under mild reaction conditions. Due to the neutral
reaction conditions, this method is compatible with acid-sensitive
protecting groups such as acetonides, carbamates, THP and TB-
DMS ethers present in the substrate.
(
Scheme).
Key words: lithium tetrafluoroborate, aldehydes, gem-diacetates
Scheme
The protection of aldehydes as gem-diacetates plays an
important role in organic synthesis because they are useful
precursors for synthetically useful acetoxy dienes and di-
The reactions proceeded smoothly at ambient temperature
and the products were obtained in excellent yields with
high chemoselectivity. Ketones such as cyclohexanone,
acetophenone and 3-pentanone did not yield any acylals
under the present reaction conditions. Furthermore, the
chemoselectivity of the present method was exemplified
by the use of ketoaldehyde (entry h). This indicates that
chemoselective protection of an aldehyde in the presence
of ketone could be achieved by this procedure. However,
the reactions did not proceed in the absence of lithium tet-
rafluoroborate. Both aromatic and aliphatic aldehydes
gave the corresponding acylals in high yields (80–93%) in
a short reaction time (3.5–7.5 h). However, aromatic alde-
hydes with electron withdrawing groups like 4-nitroben-
zaldehyde required comparatively longer reaction time to
achieve complete conversion. The products were obtained
in pure form after aqueous work-up without further
purification. Acid-sensitive substrates like furfural and
cinnamaldehyde are also protected as gem-diacetates in
high yields without the formation of any side products,
which are normally observed under strongly acidic condi-
tions. The tolerance of various functional groups under
the present reaction conditions have been examined by re-
acting the substrates bearing OPh, OMe, methylenedioxy,
nitro, and olefinic groups. The major advantage of this
procedure is in the selective protection of aldehydes as
gem-diacetates in the presence of highly acid sensitive
1
halo vinyl acetates. In addition, acylals are useful as cross-
2
linking reagents for cellulose in cotton and serve as
3
activators in the composition of the bleaching mixture
used for the treatment of wine-stained fabrics. Further-
more, gem-diacetates are useful intermediates for nucleo-
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philic substitution reactions. Due to the remarkable
stability of gem-diacetates toward a variety of reaction
conditions, they are gaining importance in organic synthe-
sis as an alternative to acetals for the protection of alde-
hydes. Generally, gem-diacetates are prepared from
aldehydes and acetic anhydride using strong Brønsted
5
6
acids or Lewis acids as catalysts. Recently, metal tri-
flates, iodine and NBS have also been employed for this
7
transformation. However, many of these methods em-
ploy strongly acidic or oxidizing conditions, expensive
and hazardous reagents and cumbersome experimental/
product isolation procedures. Furthermore, very few
methods are known for the chemoselective acetalization
of aldehydes in the presence of ketones. However, the de-
velopment of a neutral alternative would extend the scope
of this transformation. Recently, lithium tetrafluoroborate
in acetonitrile (LTAN) has emerged as a powerful reac-
tion medium for effecting various transformations includ-
ing the hydrolysis of acetals, desilylation of ethers, Diels–
8
Alder reactions and glycosidation reactions.
In line with the recent surge in activity in the use of LiBF4 acetals, cabamates, TBDMS and THP ethers, which do
as a mild Lewis acid, we report herein a simple and effi- not survive under strongly acidic conditions. Due to mild
cient procedure for the conversion of aldehydes into gem- reaction conditions employed for this transformation, a
diacetates using lithium tetrafluoroborate under neutral number of functional groups, which are capable of react-
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conditions. The treatment of benzaldehyde with acetic ing with LiBF remain intact. There are several advan-
4
anhydride in the presence of lithium tetrafluoroborate in tages in the use of LiBF for this transformation, which
4
acetonitrile at ambient temperature resulted in the forma- avoids the use of strongly acidic or basic conditions. Thus,
tion of benzal diacetate in 90% yield. In a similar fashion, this method is mild and tolerates a wide range of function-
al groups. Best results were obtained with an equimolar
ratio of LiBF , acetic anhydride, and aldehyde. Several
examples illustrating this novel and rapid procedure for
the preparation of gem-diacetates are summarized in the
Synlett 2002, No. 4, 29 03 2002. Article Identifier:
437-2096,E;2002,0,04,0604,0606,ftx,en;D21601ST.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214
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1
©

LETTER
LiBF -Mediated Conversion of Aldehydes to gem-Diacetates
605
4
Table. The gem-diacetates can be conveniently depro- In summary this paper describes a mild and efficient
tected to their parent aldehydes using aqueous potassium method for the conversion of aldehydes to gem-diacetates
6
a
carbonate under mild conditions.
using LiBF under neutral conditions thereby leaving acid
4
and base-labile protecting groups intact. The high levels
of chemoselectivity in this process combined with a sim-
ple operation, high yields and cleaner reaction profiles
will find a wider use of the diacetate-protecting group in
organic synthesis.
Table LiBF -Mediated Conversion of Aldehydes to gem-Diace-
tates
4
a
Entry Substrate
a
Product
3a
Reaction Yieldb
Time (h) (%)
Acknowledgement
4.5
4.0
5.0
90
92
93
BVS and ChV thank CSIR, New Delhi, for the award of fel-
lowships.
b
c
3b
3c
References
(
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981, 1096. (b) Snider, B. B.; Amin, S. G. Synth. Commun.
978, 8, 117.
d
e
f
3d
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4.0
3.5
4.5
89
87
90
(
(
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6
g
h
3g
3h
5.0
4.5
88
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(
Tetrahedron Lett. 2000, 41, 2695.
(
5) (a) Gregory, M. J. J. Chem. Soc. B 1970, 1201.
(
b) Freeman, F.; Karchefski, E. M. J. Chem. Eng. Data 1977,
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962.
i
j
3i
3j
5.0
7.5
90
80
(6) (a) Kochhar, K. S.; Bal, S. B.; Deshpande, R. P.;
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765. (b) Scriabine, I. Bull. Soc. Chim. Fr. 1961, 1194.
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998, 849. (b) Chandra, K. L.; Saravanan, P.; Singh, V. K.
(
(
1
k
l
3k
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4.0
85
83
Synlett 2000, 359. (c) Deka, N.; Kalita, D. J.; Borah, R.;
Sharma, J. C. J. Org. Chem. 1997, 62, 1563. (d) Karimi, B.;
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(
8) Babu, B. S.; Balasubramanian, K. K. Acros Organics Acta
2
000, 7, 1.
m
n
3m
3n
4.5
5.5
85
90
(9) Preparation of gem-Diacetates: A mixture of aldehyde (5
mmol) freshly distilled acetic anhydride (5 mmol) and LiBF4
(5 mmol) in acetonitrile (15 mL) was stirred at r.t. for an
appropriate time (Table). After complete conversion, as
indicated by TLC, the reaction mixture was poured into sat.
sodium bicarbonate solution (30 mL) and extracted with
ethyl acetate (2 15 mL). The combined organic layers were
dried over anhyd Na SO and concentrated in vacuo. The
o
p
3o
3p
5.0
4.0
85
90
2
4
resulting product was recrystallized from ethyl acetate–
hexane (2:8) to afford pure 1,1-diacetate.
1
Spectral data. 3b: Solid, mp 72–74 °C, H NMR (CDCl ):
3
q
r
3q
3r
1
5.0
4.5
85
80
= 2.18 (s, 6 H), 3.88 (s, 3 H), 3.89 (s, 3 H), 6.83 (d, 1 H,
J = 8.0 Hz), 7.03 (s, 1 H), 7.08 (d, 1 H, J = 8.0 Hz), 7.58 (s,
+
1
H). MS (EI): m/z = 268 [M ], 167, 139, 95, 77, 43. IR
(KBr): 3049, 2955, 1745, 1687, 1495, 1243, 1010, 968
–
1
6
1
cm . 3d: Solid, mp 66–67 °C (ref. 66–67). H NMR
CDCl ): = 2.15 (s, 6 H), 7.10 (dd, 1 H, J = 5.0, 4.5 Hz),
(
3
a
7.30 (d, 1 H, J = 4.5 Hz), 7.40 (d, 1 H, J = 5.0 Hz), 7.90 (s,
All products were characterised by IR, H NMR, mass spectral data
and also comparison with authentic samples.
+
1
H). MS (EI): m/z = 214 [M ], 171, 155, 112, 85. IR(neat):
–
1
b
3050, 2960, 1757, 1480, 1245, 1017, 845 cm . 3f: Solid, mp
4–85 °C (ref. 84–86). H NMR (CDCl ): = 2.15 (s, 6 H),
Isolated yields after recrystallization (ethyl acetate–hexane, 2:8).
5
1
8
3
5.95 (dd, 1 H, J = 16.5 and 7.2 Hz), 6.85 (d, 1 H, J = 16.5
Synlett 2002, No. 4, 604–606 ISSN 0936-5214 © Thieme Stuttgart · New York

6
06
J. S. Yadav et al.
Hz), 7.20–7.45 (m, 6 H). MS (EI): m/z = 234 [M ], 191, 175,
LETTER
(EI): m/z = 300 [M ], 198, 170, 142, 115, 77, 43. IR (KBr):
+
+
–
1
1
32, 101, 91. IR (KBr): 3055, 2955, 1750, 1680, 1490, 1240,
3053, 2965, 1748, 1680, 1490, 1240, 1015, 967 cm . 3k:
–1
1
6
1
1
015, 970 cm . 3h: H NMR (CDCl ): = 2.20 (s, 6 H), 7.80
Liquid, 127–129/2mm (ref. 128/2mm). H NMR (CDCl ):
3
3
(
t, 2 H, J = 8.2 Hz), 7.60 (s, 1 H), 7.65 (m, 1 H), 7.95 (d, 2
= 0.95 (t, 3 H, J = 6.8 Hz), 1.25–1.50 (m, 6 H), 1.75–1.83
(m, 2 H), 2.15 (s, 6 H), 6.70 (t, 1 H, J = 6.8 Hz). MS (EI):
+
H, J = 8.2 Hz). MS (EI): m/z = 236 [M ], 193, 105, 77, 51,
–
1
+
4
3. IR (KBr): 3055, 2970, 1760, 1720, 1235, 1020 cm . 3i:
m/z = 202 [M ], 159, 143, 100, 84. IR(neat): 3040, 2955,
1
–1
H NMR (CDCl3): = 2.16 (s, 6 H), 6.98–7.05 (m, 3 H),
.08–7.20 (m, 3 H), 7.30–7.38 (m, 3 H), 7.60 (s, 1 H). MS
1750, 1685, 1485, 1245, 1020, 965 cm .
7
Synlett 2002, No. 4, 604–606 ISSN 0936-5214 © Thieme Stuttgart · New York